Porcine OSU and Gottfried rotaviruses are distinct by neutralization and thus both their VP3 and VP7 outer capsid proteins are unrelated antigenically. In order to study these neutralization proteins a single gene substitution OSU x Gottfried porcine rotavirus reassortant (11-1) was generated by gene reassortment. This reassortant derived 10 genes (including the fourth gene encoding VP3) from the OSU strain (serotype 5) and only the ninth gene (encoding the other major neutralization glycoprotein [VP7]) from the Gottfried strain (serotype 4). Sera obtained from gnotobiotic piglets three weeks after initial oral administration of this reassortant contained high levels of neutralizing antibodies not only to Gottfried, mediated by VP7, but also to OSU, mediated by VP3. This established that VP3 is as effective an immunogen as VP7 in inducing neutralizing antibodies during experimental intestinal infection. When a group of piglets initially infected with the reassortant was challenged three weeks later with virulent Gottfried virus, complete protection was observed as indicated by failure of symptoms to develop and failure to detect virus shedding. Following challenge of another group of piglets (previously infected with the reassortant) with virulent OSU virus, complete protection against diarrhea was also observed and virus shedding was delayed in onset and decreased in duration. These observations indicate that: (i) VP3 antibodies induced during initial rotavirus infection confer resistance to disease produced by virulent rotavirus and (ii) a reassortant rotavirus bearing VP3 and VP7 neutralization antigens derived from separate rotaviruses which are distinct by neutralization induces immunity to both parental viruses.